Bioactive substances such as therapeutic agents, vaccine immunogens, and nutrients often cannot be administered in pure form, but must be incorporated into biocompatible formulations that enhance solubility of the bioactive material and package it in a suitable form to achieve optimal beneficial effects while minimizing undesirable side effects. Efficient delivery of bioactive agents is often hindered by a short clearance time of an agent in the body, inefficient targeting to a site of action, or the nature of the bioactive agent itself, for example, poor solubility in aqueous media or hydrophobicity. Thus, many formulation strategies have been developed to improve delivery, including controlled release formulations, emulsions, and liposomal preparations.
Liposomal pharmaceutical delivery systems have been described. Liposomes are completely closed, spherical lipid bilayer membranes containing an entrapped aqueous volume. The lipid bilayer includes two lipid monolayers composed of lipids having a hydrophobic tail region and a hydrophilic head region. The structure of the membrane bilayer is such that the hydrophobic, nonpolar tails of the lipid molecules orient toward the center of the bilayer while the hydrophilic heads orient toward the aqueous phases both on the exterior and the interior of the liposome. The aqueous, hydrophilic core region of a liposome may include a dissolved bioactive substance.
Delivery of pharmaceutically useful hydrophobic substances is often particularly problematic because they are insoluble or poorly soluble in an aqueous environment. For hydrophobic compounds used as pharmaceuticals, direct injection may be impossible or highly problematic, resulting in such dangerous conditions as hemolysis, phlebitis, hypersensitivity, organ failure, and/or death. There is a need for improved formulations for hydrophobic bioactive substances that will promote stability in an aqueous environment and allow efficient delivery of such substances to a desired site of action.